LEF3 phosphorylation attenuates the replication of Bombyx mori nucleopolyhedrovirus by suppressing its interaction with alkaline nuclease

Late expression factor 3 (LEF3), a multifunctional single-stranded DNA binding protein encoded by baculoviruses, is indispensable for viral DNA replication and plays a pivotal role in viral infection. Our previous quantitative analysis of phosphorylomics revealed that the phosphorylation levels of two serine residues (S8 and S25) located in LEF3 nuclear localization sequence were significantly up-regulated after Bombyx mori nucleopolyhedrovirus (BmNPV) infection, but the underlying mechanism remained unknown. To investigate the impact of phosphorylation on BmNPV infection, site-direct mutagenesis was performed on LEF3 to obtain phosphorylated mimic (S/D) or dephosphorylated mimic (S/A) mutants. The results demonstrated that the viral replication and proliferation were inhibited by phosphorylation of S8 or S25. Furthermore, we found that the N-terminal 125 amino acids region was responsible for interacting with virus-encoded alkaline nuclease, but this interaction could be suppressed by the phosphorylation. Our findings indicated that phosphorylation may serve as an antiviral strategy for host.